Radical Reactions in Domino Processes

Domino Reactions Concepts for Efficient Organic Synthesis, First Edition. Edited by Lutz F. Tietze. 

This initiation step is not included in the central chain process. However, the radical intermediate R then undergoes unimolecular rearrangement and forms R with or without the production of the side product B. Next, the domino reactions 

This whole domino sequence becomes a chain reaction, which is not absolutely required for a domino reaction. For efficiently functionahzing domino products, individual rearrangements must be faster than termination of combination, disproportionation, and redox reactions of R , and faster than their reactions with the solvent, precursor, and initiator molecules. Also, the final intermediate R should react selectively with S while the rest of the radical species do not Hence, if the final rearrangement results in changes in polarity or reactivity of the propagating radical species, the generation of versatile O-centered radicals or vinyl-type radicals for efficient domino synthesis can be made. 

In 2011, Hayashi and coworkers [14] reported an iron-catalyzed oxidative coupling of alkylamides 20 and arenes 21 to give benzylamides 25. This domino process 

Cha and coworkers [15] described an interesting example of a radical/cation-mediated domino reaction for the stereoselective preparation of bicyclo[5. B.Ojdecan-3-ones 31 using aminocyclopropane 30 as substrate which was prepared by employing an intramolecular Kulinkovich cydopropanation of olefin-tethered amide. 

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Instead of simply using two radical reactions in a domino process, the combination of three and more radical C-C- or C-N-bond forming radical transformations is also possible. This makes this methodology one of the most powerful procedures in the synthesis of complex molecules starting from simple substrates [77]. During the years, several strategies have been developed, and these are depicted in Scheme 3.50. The strategies can be classified as three types ... 

For the reason of comparison and the development of new domino processes, we have created a classification of these transformations. As an obvious characteristic, we used the mechanism of the different bond-forming steps. In this classification, we differentiate between cationic, anionic, radical, pericyclic, photochemical, transition metal-catalyzed, oxidative or reductive, and enzymatic reactions. For this type... 

Besides the numerous examples of anionic/anionic processes, anionic/pericydic domino reactions have become increasingly important and present the second largest group of anionically induced sequences. In contrast, there are only a few examples of anionic/radical, anionic/transition metal-mediated, as well as anionic/re-ductive or anionic/oxidative domino reactions. Anionic/photochemically induced and anionic/enzyme-mediated domino sequences have not been found in the literature during the past few decades. It should be noted that, as a consequence of our definition, anionic/cationic domino processes are not listed, as already stated for cationic/anionic domino processes. Thus, these reactions would require an oxidative and reductive step, respectively, which would be discussed under oxidative or reductive processes. 

In an anionic/radical domino process an interim single-electron transfer (SET) from the intermediate of the first anionic reaction must occur. Thus, a radical is generated which can enter into subsequent reactions. Although a SET corresponds to a formal change of the oxidation state, the transformations will be treated as typical radical reactions. To date, only a few true anionic/radical domino transformations have been reported in the literature. However, some interesting examples of related one-pot procedures have been established where formation of the radical occurs after the anionic step by addition of TEMPO or Bu3SnH. A reason for the latter approach are the problems associated with the switch between anionic and radical reaction patterns, which often do not permit the presence of a radical generator until the initial anionic reaction step is finished. 

A dramatic improvement in this new round trip radical domino processes developed by Curran s group was presented by Takasu, Ihara and coworkers. The new method relies on the introduction of a conjugated ester moiety at the terminal olefm, thereby effecting an acceleration of the domino reaction accompanied with an enhancement of the regio- and stereoselectivity [81]. Thus, reaction of 3-196 with Bu3SnH led to a 4 3 mixture of the two diastereomeric tricycles 3-197 and 3-198 in 83% yield. In this process, the vinyl radical 3-199 is initially formed, but this smoothly cyclizes in 5-exo-trig manner to give radical 3-200 (Scheme 3.52). Due to... 

The connection of radical and pericyclic transformations in one and the same reaction sequence seems to be on the fringe within the field of domino processes. Here, we describe two examples, both of which are highly interesting from a mechanistic viewpoint. The first example addresses the synthesis of dihydroindene 3-326 by Parsons and coworkers, starting from the furan 3-321 (Scheme 3.79) [128]. Reaction of 3-321 with tributyltin hydride and AIBN in refluxing toluene led to the 1,3,5-hexatriene 3-324 via the radicals 3-322 and 3-323. 3-324 then underwent an elec-trocyclization to yield the hexadiene 3-325 which, under the reaction conditions, aromatized to afford 3-326 in 51 % yield. 

Abstract In this chapter different types of domino-processes are described which consist of the combination of cationic, anionic, radical, pericyclic and transition metal-catalyzed as well other reactions. The methodology is used for the highly effective synthesis of carbocycles and heterocycles as well as of natural products and other interesting materials. It is also employed as an efficient tool in combinatorial chemistry. 

In a combination of photochemical cyclization and a radical reaction Yoshimatsu et al synthesized 2-azabicyclo[33.0locta-3,7-diene 169 from the trienal hydrazone 166.1891 The domino process was initiated by irradiation of 166 at 400-500 nm in benzene. The transformation may include an intermolecular [2+2]-cyclization, followed by ring opening to give... 

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